Nu-chloro compound and its use in sterilization



Patented May 8, 1934.

N-CHLOBO COMPOUND AND ITS USE IN' STEBILIZA TION Franz C.SchmelkmBloomfleld, N. 1., amino: to

Wallace & .liernan Products, Inc Belleville, N. 1., a corporation of NewJersey No Drawing. Application August 1, i933,

' Serial No. 684,121 I 17 Claims. ref-17y This invention relates tocertain new N-chloro compounds, and to the use of these compounds andother N-chloro compounds as sterilizing.

agents.

application Serial One of the principal objects of thepresent inventionis to provide sterilizing agents which will No. 632,194, filed September8,

that is, in liquids of which it may be said that they have an abnormallyhigh chlorine demand.

Other objects of the invention are to provide sterilizing agents whichare stable under all ordiv 5 (quinone) is termed the oxidant, and thereduced member (hydroquinone) the reductant. A redox system is areduction-oxidation system which is thermodynamically reversible. Inother words, theterm redox system is reserved for suchreduction-oxidation systems in which the reduction of the oxidant yieldsthe same energy as is expended upon the oxidation of the reductant. Itin such a system a definite amount of oxidant is reduced to thereductant and the reductant then reoxidized to the oxidant, the changein free energy is zero. Another important characteristic of a redoxsystem is that a definite electrode potential can be measuredin'solutions containing redox systems if an indifferent electrode isimmersed in such solu- 0 tions. This potential is dependent upon theratio of the concentrations of the constituents'only and 'not upon theirabsolute concentration. In other words, the potential which can bemeasured in a solution which contains .1 mol. fraction of reductant and.9 mol. fractions of oxidant is the same regardless of what the molarconcentration is. There are some exceptions to'this rule in such caseswhere,'in the reduction or oxidation, a-

change in the total number of molecules in the solution occurs.

Naturally, this potential is independent of whether the. mixture ofoxidant and reductant isarrived at by adding a definite amount ofreducing agent to a definite amount of oxidant or the I correspondingamount of oxidizing a ent to the corresponding amount of reductant.

oxidants of redox systems may and do have widely different structures;for example, some This application is a continuation in part of acteifectively in the presence of organic matter,

have an azo group and others a duinoid group. There is, so far as I knowat present,no way of determining by structure alonewhether,a com-' poundbelongs or does not'belong to .a redox system.

Further, mere ability to be alternately oxidized and reduced does notsignify that the substances possessing that ability necessarily belongto redox While no hard and fast rule can be laid down for determiningwhether or not a given substance belongs to a redox system, beyondtesting it to see whether it can be reversibly oxidized and reduced asabove described, I have found that all the N-chloro derivatives ofsubstances belongingto redox systems which I have been able to test acthighly effectively in liquids having an ab- 7 normally high chlorinedemand.

N-chloro derivatives of the oxidants of redox systems are in generaldistinguishable om other types of chlorine disinfecting compounds bythefact that they do not liberate iodine from neutral potassium iodidesolutions. This test requires that the substances tested be pure, orotherwise iodine may be liberated by the impurities present. Further,while all'the N- chloro derivatives of oxidants of redox systems which Ihave tested with potassium iodideshowed no liberation of iodine, theremay be such derivatives which will liberate iodine, and, if so, they arenot from such fact alone to be regarded as outside the scope of thisinvention.

degree of oxidation from each other. Converse- 100,

ly,-my compounds are characterized by the fact that they may again bereduced to one or other of the two substances mentioned above. All N-chloro derivatives which do not possess the above mentionedcharacteristics are outside of the scope m5 of :my invention. Hence,whether the initial material is the reductant' or oxidant, the flnalproduct may be regarded as a derivative of the oxidant. 1

The N-chloro derivatives of redox oxidants are remarkable for theirstability; they do not decompose spontaneously. like hypochlorites andmany other chlorine derivatives, and hence do not have any chlorinousodor. The stability of Y the N-chloro derivatives of redox oxidants may5 be due to the fact that the basic compound (the unchlorinated oxidant)is an oxidizing agent in itself. In any case, the N-chloro group inthese derivatives is dissociated to a much lesser extent than in otherN-chloro compounds, as evidenced by the reluctance of these compounds togive a free chlorine test with neutral potassium iodide and also by theabsence of chlorinous odor. The probability, therefore, of interactionbetween dissociated chlorine and acceptors thereof, be they within orwithout the molecule, is considerably reduced. This is furtheremphasized by the fact that carbon-hydrogen dissociation in quinone; forinstance, (which would provide an intramolecular acceptor fordissociated chlorine), is probably very much lower than thecarbon-hydrogen dissociation in N-chloro acetanilide, for instance,where the change from the N-chloro to the C-chloro structure of themolecule may assume explosive violence.

In spite of this unusual stability of the N-chloro derivatives of redoxoxidants against common chemical acceptors for chlorine, they areefficient as bactericides to a very surprising extent in view of theircomparative inertness in other respects. Hence, while chlorine, or suchchlorine derivatives as hypochlorites, may be said to act on nonlivingorganic matter and bacteria with about equal facility, the N-chloroderivatives of oxidan'ts of redox systems have, as it may be said, a.highly selective action on bacteria, destroying the latter while actingless strongly on non-living organic matter.

This selective action is possessed by N-chloro derivatives of redoxoxidants to a much greater extent than by N-chloro derivatives of othertypes which are themselves more selective than chlorine orhypochlorites. For instance, it requires about 125 ppm. of availablechlorine as N chloro-succinimide in a liquid containing 12 /2% normalmilk solids to show residual chlorine after 24 hours contact, and only avery slight amount of residual chlorine can be found in the liquid atthe end of such period. With certain N-chloro derivatives of redoxoxidants, a strong residual can be obtained in the same liquid after 24hours with less than ppm. of available chlorine.

' Another advantageous property of these N- chloro derivatives of redoxoxidants resulting from their general stability is that they havephysical and chemical properties which enable them to be readilymanufactured, shipped and stored in substantially pure form and withoutthe em- 7 ployment of specially constructed containers.

The N-chloro compounds forming the subject matter of the presentinvention are, therefore, admirably adapted for commercial saleanddistribution. They are stable under ordinary atmospheric conditions,except where both light I and moisture are present, and not in the leastexplosive. handled and shipped. I

- Of the N-chloro derivatives of redox oxidants fwhich I have examined,the most eflicient are the substances which may be generically termedN-chloro azo-dicarbonamidines. Such deriva' tives comprise homologues ofthe simple N-' chloro. azo-dicarbonamidine compounds.

From the formula: of the materials from which said azo products aremade, the chemical analyses of said products, and their chemicalproperties,

the generic graphic formula of such products appears to be that givenbelow:

RN.=CN=NC=NR N R: NR1

Further, being solids, they are easily" In this formula one or more Rsrepresents a chlorine atom. The other Rs usually represent hydrogen or aradical such as -CH3.

Of the above general class of N-chloro azo compounds, the most suitableappears to be N-dichloro azo-dicarbonamidine, more termed NN'-dichloroazo-dicarbonamidine. For simplicity the shorter term is used in thisspecification and claims for this and other similar compounds.

N-dichloro azo-dicarbonamidine forms needlelike yellow crystals. Thiscompound colors water in which it is dissolved strongly yellow, eventhough the actual amount of the compound in a saturated water solutionis not more thanabout 200 parts in a million at 0 C. This color is stillvery marked at much lower concentrations.-

The intense yellow color of solutions of N-dichloro-azo-dicarbonamidinedisappears as the available chlorine thereof is consumed. It ispossible, therefore, to determine by the color or tint.

Ortho-quinoid compounds r m-1 r N-monochloro-ilaphthoquinone imidc (1,2)

Para quinoid compounds N -dichloro-quinonc-diimide (1,4)

N-m0noehloro-quinonc-imiilc (1,4)

N-mon'ochlonrzo dibrom-quinone-imide properly NCl O N-monochloro-Smetbyl-qulnone-imided N -monochloro-2 metbyl quinone-imide4 0N-monochloro-Z, 6 dichlor-qulnone-imide In each of the above quinoidstructure compounds, the chlorine is attached to the amino group whichoriginally participated in the oxidation-reduction mechanism, as will beclear from the following example:

Reductant Oxidant N-chloro derivative of of N-chloro derivatives, evenby treatment of the" reductants with chlorine. Where the oxidantissufliciently stable to permit ofitsformation, an

N-chloro derivative can be formed which has a far higher stability thanthe oxidant from which it was formed. 1 have found that this holds trueof all the compounds I have prepared, namely that the N-chloroderivative is much more stable than the unchlorinated oxidant. Itfollows, therefore, that the. greater difliculty in preparing N-chloroderivatives of ortho-quinoid systems than of paraquinoid systems is dueto the far greater instability of the oxidants of the former as comparedwith those of the latter.

It will be seen that the N-chloro derivatives of oxidants may be ofeither aliphatic or aromatic redox systems. Besides being derivatives ofoxidants in redox systems, they have in common the fact that they possesa system of conjugated double bonds, wherein one or two N-chloro groupsform the beginning or end or both of the system. No other N-chloro groupis contained in the molecule of above mentioned compounds, and it is mybelief (and all of the substances I have made substantiate this) that aslong as no other such group is contained in the molecule the abovementioned characteristics of stability, absence of chlorinous 'odor,failure to liberate iodine from neutral potassium iodide andbactericidalefficiency in liquids of high chlorine demand are realized.

of oxidants, N-dichloro-azo-dicarbonamidine andN-dichloro-quinone-diimide (1, 4) are especially advantageous in thatthey contain a much higher proportion of available chlorine than suchsolid sterilizing agents as chloramine-T, di-chloramine-T andN-chloro-succinimide. Thus, N-dichloro-azo-dicarbonamidine andN-dichloroquinone-diimide (1, 4) contain, respectively, 38.8 and 40.5%of chlorine, as compared with 17.3, 29.6 and 26.6% for chloramine-T,di-chloramine-T, and N-chloro-succinimide, respectively.

I have found that ordinarily a concentration ofN-clichloro-azo-dicarbonamidine of between 25 and 250 parts per millionof aqueous liquid is suflicient to destroy all bacteria present in thewater or on objects immersed therein in less than five minutes, eventhough the liquid is highly charged with organic material, as in thecase of milk or serum.

When the N-dichloro azo compound is used as a preservative, whererapidity of bacterial destruction is-not a factor, even lowerconcentrations are efieotive.

In determining the concentrations of other N- chloro derivatives ofredox oxidants required to ive satisfactory results, due regard shouldbe given to the variations in available chlorine in the difierentderivatives and in the rate at which stoichiometrically equivalentamounts of such derivatives produce sterilization.

The solubility in water of the substances'coining within the scope ofthis invention varies widely. Some of them, for exampleN-dichloroquinone-diimide ('1, 4), is only soluble in water to .theextent of about 23 parts in a million at ordinary temperatures. on theother hand, N- dichloro-azo-dicarbonamidine is soluble to the extent ofabout 260 parts in a million at.20 C.

Where the solubility of the-compound in' water permits, it is mostconveniently used in the form of an aqueous solution. An organicsolvent, such as alcohol, may also be used, especially wherethe-compounds are sparingly soluble in water. For preparing sterilizingsolutions for use in dairies, soda fountains, etc., to sterilizeutensils, containers "and surfaces, all that is necessary in the case ofsubstances readily soluble in water is to allow water to percolateslowly through a bed of the compound, and then, if desired, dilute thesaturated solution so obtained. Where the solutions are not usedpromptly, they should be protected from the chemically active light raysby keeping such solutions 'in black or brown out a protective colloid orother agent adapted to prevent adherence of such particles. The

term emulsionis used to indicate such a mixture containing a protectivecolloidor other similar agent.

When the substances used are difflcultly soluble, their action may beslow since the rate of action will depend on the quantity of thesubstance in solution at any one time. When a 1 suspension or emulsionof suchv substances is -used, as fast as the substance is converted intosuch derivatives.

solubility of such, substance.

The N-chloro derivatives of the oxidant in a redox system may be usednot only alone but also in admixture with other substances which mayormay not be sterilizing agents; and the claims to a sterilizing agentare not to be construed as limited to the substances alone.

Some of these N-chloro derivativespf redox oxidants, such as theN-chloro azo-dicarbonamidines, may also be used as an antisepticdressing for the skin, cuts or mucous tissue, as

they are not irritating to the human tissues and arealmost tasteless andodorless. compounds in question, .such as the N-chloroazodicarbonamidines, are hemolytic only to a very slight degree andtherefore adapted to be injected into the blood stream.

These derivatives are destructive to molds and the like, aswell as tobacteria. They are therefore suitable for the treatment of fruit, grass,

and all other vegetable materials requiring destruction or arrest ofgrowth of micro-organisms during any stage of development or storage.

For the purposes of this patent application, no distinction is beingmade between a fungicide, a germicide, a bactericide, an antiseptic, adisinfectant, a preservative, a prophylactic and a sterilizing agent,and the expression sterilizing agent", where it is used, is meant tocomprise the above list of terms.

. Further, they term sterilization is used in its practical sense toinclude sterilization to a degree satisfactory'for the purpose for whichthe reagent is employed, and is not to be confined to sterilization inthe strict scientific sense of absolute destruction of all forms oflife, dormant or otherwise. The degree of, sterilization effecteddepends largely on the strength of the sterilizing solutions used. I

N-chloro derivatives of azo-dicarbonamidine do not attack brass orcopper, as do solutions of chlorine, chloramines or nitrogentrichloride. Iron and aluminum are attacked, however, by Such attackcan, however, be substantially, if not completely, eliminated withoutsubstantial loss of sterilizing power by the addition to suchsterilizing agent of trisodium phosphate, Na3PO4; disodium phosphate,Na2HPO4; or sodium silicate, Nazsios; or generally salt mixturescontaining phosphates or silicates. The proportion of phosphate orsilicate added shouldbe suflicient to reduce the percentage of availablechlorine in the dry mixture not more than about 5%. For example, usingN-dichloro-azo-dicarbonamidine contains about 39% of available chlorine,the proportion of phosphate or silicate to such N- dichloro compoundshould be at least 7 1.

So far as N-chloro-azo-dicarbonamidines are concerned, I believe that Iam the first, not merely to discover their beneficial properties asabove described, but also to discover the compounds themselves. Suchcompounds and the processes for making them are claimed in my copendingapplication Serial No. 632,193, filed September excess of the" Some ofthewhich 8, 1932. A method for making N-dichloro-azodicarbonamidinesubstantially quantitatively comprises mixing a 10 to solution ofhydrazo-dicarbonamidine hydrochloride with a neutral solution of sodiumhypochlorite and filtering off' the precipitatedN-dichloro-azo-dicarbonamidine. The temperature of the solutions duringreaction should be between 0 and 5 C. The'reacting materials should beused in the proportions called for by the following equation:

What is claimed is: 1. As a sterilizing agent, a solution of an N-chloro derivative of the oxidant in a redox system.

2. As a; sterilizing agent, an N-chloro aliphatic compound having aselective action for bacteria in the presence of oxidizable organicmatter and sufliciently stable so as not to possess any chlorinous odor.

3. As a sterilizing agent, a solution of an N- chloro derivative of anoxidant in a redox system wherein all the oxidizing chlorine is bound tonitrogen atoms constituting part of a conjugated system of double bonds.

4.As a sterilizing agent, an N-chloro derivative of an oxidant in analiphatic redox system.

5. As a sterilizing agent, an N-chloro-azo-dicarbonamidine.

6. As a sterilizing agent, N-diehloro-azo-dicarbonamidine.

7. As a sterilizing agent, a solution of an'N- chloro derivative of anoxidant in an aromatic redox system.

8. As a sterilizing agent, a solution of an N- chloro derivative of theoxidant in a redox system wherein the chlorine is attached to the aminogroup which originally participated in the oxidation-reductionmechanism.-.

9. As a sterilizing agent, a solution of an N- chloro derivative of theoxidant in a redox system of para-quinoid structure.

with at least two hydrogens replaced by chlorine.

